RESUMO
To investigate the possible effects of α-tocopherol on erythrocyte membrane adenosine triphosphatases against radiation damage in oral cancer patients. Adenosine triphosphatase activities were analysed in oral cancer patients before and after radiotherapy (at a dosage of 6000 cGY in five fractions per week for a period of six weeks) and after supplemented with α-tocopherol (400 IU per day for entire period of radiotherapy). The membrane bound enzymes such as Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and some trace elements were altered in oral cancer patients before and after radiotherapy. Supplemented with α-tocopherol modulates the erythrocyte membrane which is damaged by radiotherapy which suggests that α-tocopherol protects the erythrocyte membrane from radiation damage in oral cancer patients.
Assuntos
Adenosina Trifosfatases/metabolismo , Membrana Eritrocítica/enzimologia , Neoplasias Bucais/radioterapia , Lesões por Radiação/prevenção & controle , alfa-Tocoferol/uso terapêutico , Adenosina Trifosfatases/efeitos dos fármacos , Adenosina Trifosfatases/efeitos da radiação , Adulto , Idoso , ATPase de Ca(2+) e Mg(2+)/efeitos dos fármacos , ATPase de Ca(2+) e Mg(2+)/metabolismo , ATPase de Ca(2+) e Mg(2+)/efeitos da radiação , Suplementos Nutricionais , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/enzimologia , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/efeitos da radiação , Fatores de Tempo , alfa-Tocoferol/administração & dosagemRESUMO
Diabetes leads to modification of collagen such as advanced glycation and cross-linking which play an important role in the pathogenesis of diabetes mellitus. We have investigated the effect of green tea on modification of collagen in streptozotocin (60 mg/kg body weight) induced diabetic rats. To investigate the therapeutic effect of green tea, treatment was begun six weeks after the onset of diabetes and green tea extract (300 mg/kg body weight) was given orally for 4 weeks. The collagen content, extent of advanced glycation, advanced glycation end products (AGE) and cross-linking of tail tendon collagen were investigated. Green tea reduced the tail tendon collagen content which increased in diabetic rats. Accelerated advanced glycation and AGE in diabetic animals, as detected by Ehrlich's-positive material and collagen linked fluorescence respectively were reduced significantly by green tea. The solubility of tail tendon collagen decreased significantly in diabetic rats indicating a remarkable increase in the cross-linking, whereas green tea increases the solubility of collagen in diabetic rats. The present study reveals that green tea is effective in reducing the modification of tail tendon collagen in diabetic rats. Thus green tea may have a therapeutic effect in the treatment of glycation induced complications of diabetes.
Assuntos
Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Chá/química , Tendões/metabolismo , Animais , Glicemia/metabolismo , Cafeína/análise , Cafeína/farmacologia , Catequina/análise , Catequina/metabolismo , Catequina/farmacologia , Colágeno/química , Fluorescência , Masculino , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , SolubilidadeRESUMO
The enhanced myocardial collagen content, collagen glycation and the resulting advanced glycation end products (AGE) which exhibit the characteristics of increased cross-linking are proposed for the stiffness of myocardium in diabetes. To explore the cardioprotective effect of green tea in diabetes, we study the effect of green tea extract on myocardial collagen characteristics in streptozotocin diabetic rats. The effect of green tea on marker enzymes in serum and cardiac tissues were also assayed to understand the extent of protection. Six weeks after the diabetes induction, diabetic rats were treated with green tea extract [300 mg (kg body weight)(-1)day(-1)] for 4 weeks. AGE were determined by fluorescence assay and cross-linking of collagen by solubility measurement while collagen content was measured by biochemical assay. The activities of aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemical assay. The increase in blood glucose, glycated hemoglobin and systolic blood pressure in diabetic rats were reduced upon green tea treatment. The activities of AST, LDH and CPK were significantly increased in serum whereas decreased in cardiac tissues in diabetic rats representing the cardiac damage. Administration of green tea to diabetic rats significantly ameliorates these enzyme activities. There was no significant difference in the myocardial collagen content among the experimental rats. A significant (P<0.05) increase in collagen linked Maillard-type fluorescence and decrease in collagen solubility in the myocardium of diabetic rats as compared to control rats (0.955+/-0.02 versus 0.683+/-0.04 and 30+/-1.41 versus 45.17+/-1.17, respectively) indicates the increase in advanced glycation end products formation and degree of collagen cross-linking. Green tea administration to diabetic rats significantly (P<0.05) decreased the fluorescence (0.73+/-0.02) whereas increased the solubility of collagen (41.5+/-1.04) indicating the reduction in advanced glycation end products and collagen cross-linking. The present study reveals that green tea by ameliorating myocardial collagen characteristics may provide a therapeutic option in the treatment of cardiovascular complications of diabetes.
Assuntos
Camellia sinensis , Fármacos Cardiovasculares/farmacologia , Colágeno/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiopatias/tratamento farmacológico , Hipoglicemiantes/farmacologia , Reação de Maillard , Miocárdio/metabolismo , Animais , Aspartato Aminotransferases/sangue , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cafeína/análise , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/uso terapêutico , Catequina/análise , Colágeno/química , Creatina Quinase/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Fibrose , Hemoglobinas Glicadas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Glicosilação/efeitos dos fármacos , Cardiopatias/etiologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , L-Lactato Desidrogenase/sangue , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Wistar , Solubilidade , Espectrometria de Fluorescência/métodosRESUMO
Lipid peroxidation is believed to play an important role in pathogenesis of diseases. 4-Nitroquiunoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, was found to induce lipid peroxidation in vivo and in vitro. Green tea contains high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GP) can play a protective role in 4-NQO induced in vitro lipid peroxidation. 4-NQO at the concentration of 1.5 mM was found to induce lipid peroxidation in 5% liver homogenate in phosphate buffered saline and extent of lipid peroxidation at the different time intervals 0, 15, 30 and 45 min where studied by assessing parameters such as hydroxyl radical production (OH), thiobarbituric acid reactants (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). It was found that addition of 4-NQO caused an increase in OH and TBARS level and a decrease in activity of SOD, CAT and the levels of GSH. Simultaneous addition of GP 10 mg/ml significantly decreased lipid peroxidation and increased in antioxidant status. Thus, we conclude that GP, a potent antioxidant, was found to nullify 4-NQO induced lipid peroxidation in vitro and 4-NQO acts initially by causing oxidative stress and leads to carcinogenesis.
Assuntos
4-Nitroquinolina-1-Óxido/toxicidade , Camellia sinensis/química , Flavonoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fenóis/farmacologia , Animais , Catalase/metabolismo , Flavonoides/isolamento & purificação , Glutationa/metabolismo , Radical Hidroxila/metabolismo , Técnicas In Vitro , Peróxidos Lipídicos/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Masculino , Fenóis/isolamento & purificação , Folhas de Planta/química , Polifenóis , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Diabetes-induced hyperlipidemia, oxidative stress and protein glycation impair cellular calcium and sodium homeostasis associated with abnormal membrane-bound enzyme activities resulting in cardiac dysfunction in diabetes. To explore the cardioprotective mechanism of green tea in diabetes, we measured the changes in the levels of calcium, sodium, potassium and the activities of Na+/K+ -ATPase and Ca2+ -ATPase in green tea treated diabetic rat hearts. The effect of green tea on triglycerides, lipid peroxidation and protein glycation in diabetic heart were also measured to elucidate the underlying mechanisms. Diabetes was induced by streptozotocin (STZ, 60 mg/kg i.p.). Six weeks after the induction of diabetes, some of the diabetic rats were treated orally with green tea extract (GTE) (300 mg/kg/day) for 4 weeks. GTE produced reduction in blood glucose and lowered the levels of lipid peroxides, triglycerides and extent of protein glycation in the heart of diabetic rats. GTE blunted the rise in cardiac [Ca2+] and [Na+] whereas increased the activities of Ca2+ -ATPase and Na+/K+ -ATPase in diabetic rats. In conclusion, the data provide support to the therapeutic effect of GTE and suggest that a possible mechanism of action may be associated with the attenuation of the rise in [Ca2+] and [Na+] by ameliorating Ca2+ -ATPase and Na+/K+ -ATPase activities.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Camellia sinensis/química , Diabetes Mellitus Experimental/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Coração/efeitos dos fármacos , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Dislipidemias/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Glutationa/metabolismo , Glicosilação/efeitos dos fármacos , Coração/crescimento & desenvolvimento , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Masculino , Miocárdio/enzimologia , Miocárdio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Potássio/metabolismo , Ratos , Ratos Wistar , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Triglicerídeos/metabolismoRESUMO
Green tea polyphenols (GTP) has been used as a chemopreventive agent world wide against chemically induced cancer. The present study is aimed to understand the therapeutic action of GTP on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide (4-NQO)-induced oral cancer over a period of 30 days at 200mg/kg, p.o., Oral cancer was induced by painting 4-NQO for 8 weeks followed by administration of GTP after 22 weeks, for 30 days. Glycoconjugates such as hexose, hexosamine, sialicacid, fucose and mucoprotein were analysed. Expression of glycoconjugates was examined through histology and SDS-PAGE. Immunological markers such as circulating immune complex and mast cell density were studied. Oral cancer-induced animals showed a significant increase in levels of glycoconjugates and its expression, similar to that observed for immunological markers. Treatment with GTP altered the expression of glycoconjugates as well as immunological markers. The results suggest that GTP modulates both the expression of glycoconjugates and immunological markers resulting in regression of oral cancer.
Assuntos
Camellia sinensis/química , Flavonoides/uso terapêutico , Glicoconjugados/metabolismo , Imunoglobulinas/sangue , Neoplasias Bucais/tratamento farmacológico , Fenóis/uso terapêutico , 4-Nitroquinolina-1-Óxido/toxicidade , Fosfatase Ácida/metabolismo , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Glucuronidase/metabolismo , Hexoses/metabolismo , Masculino , Boca/efeitos dos fármacos , Boca/metabolismo , Boca/patologia , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/metabolismo , Mucoproteínas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Fosfolipases/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Polifenóis , Ratos , Ratos Wistar , Língua/efeitos dos fármacos , Língua/metabolismo , Língua/patologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , beta-Galactosidase/metabolismoRESUMO
Hyperglycemia induced oxidative stress has been proposed as a cause of many complications of diabetes including cardiac dysfunction. The present study depicts the therapeutic effect of green tea extract on oxidative stress in aorta as well as heart of streptozotocin diabetic rats. Six weeks after diabetes induction, green tea was administered orally for 4 weeks [300 mg (kg body weight)(-1) day (-1)]. In aorta and heart of diabetic rats there was a significant increase in the activity of superoxide dismutase, catalase and glutathione peroxidase with an increase in lipid peroxides. Diabetic rats showed a significant decrease in the levels of serum and cardiac glutathione. Green tea administration to diabetic rats reduced lipid peroxides and activity of antioxidant enzymes whereas increased glutathione content. The results demonstrate that the induction of antioxidant enzymes in diabetic rats is not efficient and sufficient to reduce the oxidative stress. But green tea by providing a competent antioxidative mechanism ameliorates the oxidative stress in the aorta and heart of diabetic rats. The study suggests that green tea may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.
Assuntos
Aorta/efeitos dos fármacos , Camellia sinensis/química , Diabetes Mellitus Experimental/prevenção & controle , Coração/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Antioxidantes/metabolismo , Aorta/enzimologia , Aorta/metabolismo , Comportamento Animal/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Catequina/análogos & derivados , Catequina/análise , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Glutationa/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/metabolismo , Masculino , Miocárdio/enzimologia , Miocárdio/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
1. The therapeutic effect of green tea extract (GTE) on the aortic collagen content and its characteristics were investigated in streptozotocin diabetic rats. 2. Diabetes was induced in rats by a single intra peritoneal injection of streptozotocin (60 mg/kg bodyweight). Six weeks after diabetes induction, GTE was administered orally for four weeks (300 mg/kg bodyweight daily). Systolic blood pressure, blood glucose, anti-oxidant status, collagen content, extent of glycation, collagen linked fluorescence and aortic collagen solubility pattern were determined in experimental rats. 3. At the end of the experimental period, there was a significant increase in the systolic blood pressure and blood glucose in diabetic rats. The lipid peroxides increased whereas glutathione and vitamin C levels were decreased in the serum of diabetic rats. The collagen content, extent of glycation, the advanced glycation end products (AGEs) and degree of cross-linking were increased in the aorta of diabetic rats. 4. The oral administration of GTE to diabetic rats significantly reduced the systolic blood pressure and blood glucose. The level of lipid peroxides reduced and the content of glutathione and vitamin C increased in the serum of GTE treated diabetic rats. Green tea extract also impede the accumulation of aortic collagen, extent of glycation, formation of AGEs and cross-linking of collagen in diabetic rats. The antihyperglycemic, anti-oxidant and antiglycating effects of GTE ascribed for these beneficial effects. In conclusion, green tea may have therapeutic effect in the treatment of cardiovascular complications characterized by increased AGE accumulation and protein cross-linking associated with diabetes.
Assuntos
Aorta/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Chá , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colágeno/química , Reagentes de Ligações Cruzadas , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hidroxiprolina/metabolismo , Masculino , Ratos , Ratos Wistar , Solubilidade , Espectrometria de FluorescênciaRESUMO
In cancer, a high flux of oxidants not only depletes the cellular thiols, but damages the whole cell as well. Epidemiological studies suggest green tea may mitigate cancers in human and animal models for which several mechanisms have been proposed. In the present investigation, the levels of cellular thiols such as reduced glutathione (GSH), oxidised glutathione (GSSG), protein thiols (PSH), total thiols, lipid peroxidation product conjugated dienes and the activity of gamma glutamyl transferase (GGT) were assessed in tongue and oral cavity. In 4-Nitroquinoline 1-oxide- (4-NQO) induced rats, there was a decrease in the levels of GSH, PSH and total thiols and an increase in the levels of GSSG, conjugated dienes and the activity of GGT. On supplementation of green tea polyphenols (GTP) for 30 days (200 mg/kg) for the oral cancer-induced rats, there was a moderate increase in the levels of GSH, PSH and total thiols and a decrease in the levels of GSSG, conjugated dienes and the activity of GGT. Thus, GTP reduces the oxidant production thereby maintains the endogenous low molecular weight cellular thiols in oral cancer-induced rats. From the results, it can be concluded that GTP supplementation enhances the cellular thiol status thereby mitigate oral cancer.